Abstract
Chronic cocaine administration can produce tolerance or sensitization to locomotor activating effects, depending on the treatment paradigm. The effects of chronic, continuous cocaine were measured on locomotor activity for 1 hr daily for 7 days. Cocaine produced significant increases in locomotor activity 4 hr after osmotic minipumps were implanted, and an even higher level of activity after 24 hr. This was likely a rapid sensitization to the locomotor activating effects of cocaine, because neither brain nor plasma levels of cocaine were significantly altered over the treatment period. By day 4, activity levels diminished, but remained significantly higher than in saline-treated animals. Twenty-four hr after pump removal, there were no changes in dopamine D1 or D2 receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic naltrexone produced a slight, nonsignificant decrease in locomotor activity and when combined with cocaine, produced the same pattern of activity as cocaine alone, but with slightly less stimulation on all days. Morphine produced a smaller increase in activity than cocaine that remained constant throughout the treatment week. Cocaine with morphine was additive, producing greater activity and less tolerance than cocaine alone. Thus, continuous cocaine administration produces a rapid sensitization that is lost over the course of the treatment period, yet does not produce any immediate alterations in dopamine receptors or regulation of adenylyl cyclase. The pattern of behavior is not altered by an opioid antagonist, while the sensitization period appears to be prolonged in the presence of an opioid agonist.
Footnotes
-
Send reprint requests to: Dr. Sari Izenwasser, Department of Neurology, Univ. of Miami Sch. of Med., 1501 NW 9th Avenue, Room 4061, Miami, FL 33136.
-
↵1 This work was supported by the National Institute on Drug Abuse Intramural Research Program.
- Abbreviation:
- [3H] SCH 23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2
- 3,4,5-tetrahydro-1H-3-benzazepine). cAMP (Adenosine 3′,5′cyclic phosphate
- Received August 19, 1997.
- Accepted December 8, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|